This invention relates to an improvement in preserving stability of an intravenously administrable human gamma-globulin dry preparation obtainable by polyethylene glycol fractionation of the human plasma.
Polyethylene glycol (hereinafter referred to as PEG) is a substance widely used as a stabilizer or a precipitant for protein and, because of its extremely low toxicity, is used also in the preparation of biological pharmaceuticals. For example, Polson et al has purified .gamma.-globulin by adding to human plasma PEG to a certain concentration and separating the precipitated protein (U.S. Pat. No. 3,415,804). The intravenously administrable .gamma.-globulin preparation is prepared by lyophilizing the product obtained by PEG fractionation mentioned above. But, when the lyophilized preparation is dissolved in distilled water for injection use at the time of administration, it often does not go into solution rapidly.
Some of the present inventors made an extensive study on this point and found that the dissolving velocity was affected by PEG and that when the content of contaminating PEG was below a specified level the dry preparation had an improved water-solubility to dissolve rapidly in water, and proposed a method of producing a plasma protein preparation based on this novel information (Japanese Patent Application No. 8911/83). The feature of the prior invention comprises, in a plasma protein dry preparation comprising human plasma protein prepared by PEG fractionation method, removing PEG prior to drying treatment so as to give a PEG concentration of 0.05% W/V or less when the preparation is dissolved in water to give a protein concentration of about 20% W/V.
When the content of PEG in .gamma.-glogulin preparation obtainable by fractionation by use of PEG is decreased, the stability of the .gamma.-globulin against deterioration with time becomes poor accompanied by the decrease in antibody titer and increase in anticomplement activity. It was found out that this tendency can be prevented markedly by addition of a sufficient amount of glucose for stabilizing the .gamma.-globulin to an aqueous solution of .gamma.-globulin followed by lyophilization.